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Background  

Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models.  相似文献   
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Calligrapha (Coleoptera: Chrysomelidae) is a genus with species present in most of the American continent, from the Arctic polar circle to the Pampas in Argentina. In its current concept, the genus comprises some 80 species, but the diagnosis of the genus is problematic, based on a combination of potentially symplesiomorphic character states. In this study, we investigate the largest taxonomic sample of Calligrapha diversity to date (43 species) using a phylogenetic perspective based on more than 6000 molecular characters from eight genes (four mitochondrial and four nuclear) for a systematic evaluation of the genus. The analyses also include thirteen species in the closely related Zygospila (currently a subgenus of Zygogramma) to assist the systematic delimitation of Calligrapha. Partitioned and total evidence phylogenetic trees were additionally used for molecular clock analyses and dating based on standard mtDNA evolutionary rates, and for likelihood‐based inference of ancestral areas. Calligrapha and Zygospila are reciprocally paraphyletic, and our interpretation of taxonomic stability merges both taxa into a larger genus Calligrapha which plausibly originated in the dry steppes of southern North America in the Late Miocene. The genus includes a minimum of five strongly supported lineages which initially diversified in the Pliocene, fully congruent with expectations from morphology, but of uncertain mutual relationships. Only two of these lineages dispersed to South America: the group of C. polyspila right at the time of the final closure of the Isthmus of Panama in the Early Pliocene and the group of C. argus only in recent times, well in the Pleistocene. The most species‐rich lineage of Calligrapha, associated to trees and shrubs typical of riverine and lacustrine environments (as opposed to herbaceous steppe plants, generally Malvaceae and Asteraceae, for most other groups) diversified and spread in North America in the Late Pliocene. The ecological shift to a stable habitat spreading in the continent due to climate change is hypothesized as one possible explanation for the evolutionary success of this group.  相似文献   
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Contemporary taxonomic work on New Caledonian Eumolpinae (Chrysomelidae) has revealed their high species richness in this Western Pacific biodiversity hotspot. To estimate total species richness in this community, we used rapid DNA‐based biodiversity assessment tools, exploring mtDNA diversity and phylogenetic structure in a sample of 840 specimens across the main island. Concordance of morphospecies delimitation with units delimited by phenetic and phylogenetic algorithms revealed some 98–110 species in our sample, twice as many as currently described. Sample‐based rarefaction curves and species estimators using these species counts doubled this figure (up to 210 species), a realistic estimate considering taxonomic coverage, local endemism, and characteristics of sampling design, amongst others. New Caledonia, compared with larger tropical islands, stands out as a hotspot for Eumolpinae biodiversity. Molecular dating using either chrysomelid specific rates or tree calibration using palaeogeographical data dated the root of the ingroup tree (not necessarily a monophyletic radiation) at 38.5 Mya, implying colonizations after the Cretaceous breakage of Gondwana. Our data are compatible with the slowdown in diversification rates through time and are also consistent with recent faunal origins, possibly reflecting niche occupancy after an initial rapid diversification. Environmental factors (e.g. soil characteristics) seemingly played a role in this diversification process. © 2013 The Linnean Society of London  相似文献   
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The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV α chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis.  相似文献   
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Background aims

Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.

Methods

We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 106 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients. Clinical scales, urodynamic, neurophysiological and neuroimaging studies were performed previous to treatment and at the end of the follow-up.

Results

The treatment was well-tolerated, without any adverse event related to MSC administration. Patients showed variable clinical improvement in sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction, regardless of the level or degree of injury, age or time elapsed from the SCI. In the course of follow-up three patients, initially classified as ASIA A, B and C, changed to ASIA B, C and D, respectively. In urodynamic studies, at the end of follow-up, 66.6% of the patients showed decrease in postmicturition residue and improvement in bladder compliance. At this time, neurophysiological studies showed that 55.5% of patients improved in somatosensory or motor-evoked potentials, and that 44.4% of patients improved in voluntary muscle contraction together with infralesional active muscle reinnervation.

Conclusions

The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity.  相似文献   
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Tonalli A (TnaA) is a Drosophila melanogaster protein with an XSPRING domain. The XSPRING domain harbors an SP-RING zinc-finger, which is characteristic of proteins with SUMO E3 ligase activity. TnaA is required for homeotic gene expression and is presumably involved in the SUMOylation pathway. Here we analyzed some aspects of the TnaA location in embryo and larval stages and its genetic and biochemical interaction with SUMOylation pathway proteins. We describe that there are at least two TnaA proteins (TnaA130 and TnaA123) differentially expressed throughout development. We show that TnaA is chromatin-associated at discrete sites on polytene salivary gland chromosomes of third instar larvae and that tna mutant individuals do not survive to adulthood, with most dying as third instar larvae or pupae. The tna mutants that ultimately die as third instar larvae have an extended life span of at least 4 to 15 days as other SUMOylation pathway mutants. We show that TnaA physically interacts with the SUMO E2 conjugating enzyme Ubc9, and with the BRM complex subunit Osa. Furthermore, we show that tna and osa interact genetically with SUMOylation pathway components and individuals carrying mutations for these genes show a phenotype that can be the consequence of misexpression of developmental-related genes.  相似文献   
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